Certain pyridylphosphates,thiophosphates,phosphonates and thiophosphonates

ABSTRACT

PHOSPHORIC DERIVATIVES CONTAINING SUBSTITUTED METHYLPYRIDINES AND HAVING THE GENERAL FORMULA   2-(CH3-),4-R4,5-(R2-O-P(=X)(-R1)-O-),6-R3-PYRIDINE   AND THEIR USE IN INSECTICIDAL, ACARICIDAL AND NEMATICIDAL COMPOSITIONS.

3,790,582 CERTAIN PYRIDYLPHOSPHATES, THIOPHOS- PHATES, PHOSPHONATES ANDTHIOPHOS- PHONATES Daniel Demozay, Villeurbanne, and Daniel Pillon andJacques Ducret, Lyon, France, assignors to Pepro, Societe pour leDeveloppemeut et la Vente de Specialites Chimiques, Lyon, France NoDrawing. Filed June 28, 1971, Ser. No. 157,636

Claims priority, application France, June 30, 1970, 7024078 Int. Cl.C07d 31/50 US. Cl. 260-294.8 K 9 Claims ABSTRACT OF THE DISCLOSUREPhosphoric derivatives containing substituted methylpyridines and havingthe general formula R4 R1 X R3 N/ CH:

and their use in insecticidal, acaricidal and nematicidal compositions.

R CH:

wherein R is an alkyl, alkoxy, containing from 1 to 4 carbon atoms,halogenoalkyl, alkylamino, dialkylamino, phenyl, phenoxy radical inwhich the alkyl group contains 1 to 4 carbon atoms; R is an alkylradical containing from 1 to 4 carbon atoms, which maye be halogenated;R and R are identical or different, and selected from hydrogen, halogen,nitro, or cyano, but in which both cannot be hydrogen; and X is oxygenor sulfur.

Phosphorus derivatives containing one pyridinic radical in theirmolecule are already known, and some of them have been reported ashaving advantageous insecticide properties, namely those described inFrench Pat. No. 1,063,067 dated Apr. 19, 1962.

We have discovered a series of new compounds wherein thephosphorous-containing radical is attached in the 3 position to thepyridinic ring, while having a methyl radical in the 6 position and may,besides, have substituents in the 2-4 position of said pyridinicnucleus. Said compounds have insecticidal and acaricidal properties muchmore advantageous than the derivatives described in the above-mentionedpatent.

In general, the compounds of this invention are prepared by allowing achloride of phosphoric, phosphonic, thiophosphoric, or phosphoramidicacid to react with a substituted hydroxy 3 methyl 6 pyridine, in theUnited States Patent presence of a hydracid acceptor, or with one of thesalts of the hydroxypyridine. The reaction is preferably carried out inthe presence of organic solvents, such as ketones, alcohols, aromatic oraliphatic hydrocarbons. In general, a reaction temperature is selectedwithin the range of 20 C. to C.

The following examples, which are given by way of illustration, but notby way of limitation, show the method for preparing substitutedhydroxypyridines (Examples l 5) on the one hand, and the preparation ofthe phosphoric esters (Examples 6-12) on the other hand.

EXAMPLE I Chloro-2-hydroxy-3-methyl-6-pyrid,ine

water until the 01- ions are eliminated, and then dried.

Weight obtained g 125 Melting point C-.." 198 Yield perce Saidprecipitate recrystallized in ethanol melts at 199 C.

Analysis.Calculated for C H CINO (percent): C, 50.17; H, 4.18; N, 9.75;Cl, 24.74. Found (percent): C, 50.22; H, 4.06; N, 9.64; CI, 24.64.

EXAMPLE 2 Bromo-2-hydroxy-3-methyl-6-pyridine 32 g. (0.2 M) of brominein solution in 200 ml. of pyridine are poured onto 21.8 g. (0.2 M) ofhydroxy-3- methyl-6-pyridine in solution in ml. of pyridine. Thereaction is allowed to proceed for 5 hours at ambient temperature.

The solution is neutralized with'0.2 M of soda, and the pyridine isremoved by steam distillation. Precipitates form in the remainingsolution upon cooling. The precipitate is washed and dried. It is black,and its melting point is not well defined. It is dissolved in ml. ofethanol, and treated with bone black. After filtering and cooling thesolution, a light beige precipitate is obtained.

An'alysis.-Calculated for CSHGBI'NO (percent): C, 38.29; H, 3.19; N,7.44; Br, 42.44. Found (percent): C, 38.25; H, 3.02; N, 7.37; Br, 42.37.

3 EXAMPLE 3 Iodo-2-hydroxy-3-methyl-6-pyridine 109 g. (1 M) ofhydroxy-3-methyl-6-pyridine are suspended in 500 ml. of distilled watercontaining 150 g. of sodium carbonate, 280 g. (1.1 M) of iodine aredissolved in 2 l. of distilled water by means of 280 g. of potassiumiodide, and added to the suspension at ordinary temperature, after whichthe reaction is allowed to proceed for 2 hours at room temperature.

The resulting precipitate is filtered. It is then dissolved in 2 l. ofsoda solution containing 25 g./l., and treated at boiling with boneblack for 15 minutes. After filtering, the solution is cooled, and thenneutralized with 80 ml. of acetic acid.

The light beige precipitate thus obtained is filtered and dried.

Weight g 180 Melting point C 195-198 Yield "percent..- 77

Recrystallized in ethanol, it melts at 203 C.

Analysis.Calculated for C H INO (percent): C,

30.63; H, 2.55; N, 5.95; I, 54.04. Found (percent): C, 30.84; H, 2.46;N, 5.89; I, 54.17.

EXAMPLE 4 Chloro-2-hydroxy-3-nitro-4-methyl-6-pyridine n. or

N 10 m1. of red fuming nitric acid are added slowly to 14.35 g. (0.1 M)of chloro-2-hydroxy-3-methyl-6-pyridine dissolved in 50 ml. of strongsulfuric acid. The reaction mixture is then heated for 15 hours at 50 C.It is then poured onto 200 g. of cracked ice, and neutralized to pH 3with 215 ml. of ammonia. The resulting yellow precipitate is filteredand dried.

Weight -d g 7 Melting point C 76 Yield percent" 37 H NLCI 12.5 g. (0.06M) of phosphorus pentachloride are added in increments to 7.5 g. (0.04M) of chloro-2-hydroxy-3-nitro-4-methyl-6-pyridine in solution in 50 ml.of phosphorus oxychloride. The solution is refluxed until the gasevolution ceases (30 minutes), and then allowed to stand overnight. Itis then decomposed over 200 ml. of water, and neutralized with 210 ml.of strong soda. As the resulting precipitate is brown and has a very lowmelting point, it is recrystallized in 0 ml. of distilled water. Itsmelting point is then 138 C., but the yield of the reaction is very low:11.2%. Weight obtained: 0.8 g.

Analysis-Calculated for C H Cl NO (percent): C, 40.44; H, 2.80; N, 7.86;CI, 39.88. Found (percent): C, 7. 2; C 3 .8.9.

4 EXAMPLE '6 O-O-dimethyl and 0-3 (iodo-2-methyl-6)pyridyl phosphate P-OCHaO The sodium ethoxide prepared from 0.7 g. (0.03 M) of sodium and 40ml. of absolute alcohol is added to 7.05 g. ofiodo-Z-hydroxy-3-methyl-6-pyridine (0.03 M) in solution in 40 ml. ofabsolute alcohol. The reaction is continued for one hour at roomtemperature. 4.35 g. of dimethylchlorophosphate (0.03 M) are then addedat room temperature, and the mixture is refluxed for one hour.

The sodium chloride is filtered OE and the alcohol is removed. Theresidue is taken up with 100' ml. of chloroform, and washed once withm1. of 5% sodium bicarbonate, and twice with 80 m1. of distilled water,and then dried with magnesium sulfate. The chloroform is removed underwater pump vacuum, and then under high vacuum during one hour. The oilthus obtained is of light brown color.

Analysis-Calculated for C H INO P (percent): C, 27.98; H, 3.20; N, 4.08;P, 9.03. Found (percent): C, 27.80; H, 3.3 0; N, 3.91; P, 8.89.

EXAIVIPLE 7 O-methyl and 0-3 (nitro-2-methyl-6)pyridyl methylphosphateCHzO CH3 N/ The sodium ethoxide prepared from 1.15 g. (0.05 M) of sodiumand 40 ml. of absolute alcohol is added to 7.7 g. ofnitro-2-hydroxy-3-methyl-6-pyridine (0.05 M) in solution in 40 ml. ofabsolute alcohol. The reaction is continued for one hour at roomtemperature. 6.4 g. (0.05 M) of O-methy1-methylchlorophosphinate arethen added at ordinary temperature, after which the mixture is refluxedfor one hour.

The sodium chloride is then filtered off, and the alcohol removed. Theresidue is taken up with ml. of chloroform, and washed once with 80 ml.of 5% sodium bicarbonate and twice with 80 ml. of distilled water, andthen dried over magnesium sulfate. The chloroform is then removed, and araw light yellow oil is obtained.

Weight g 8.8 1.5145 Yield percent 71.5

The sodium ethoxide, prepared from 0.9 g. (0.04 M) of sodium and 40 ml.of absolute alcohol, is added to 5.75 g. ofchloro-2-hydroxy-3-methyl-6-pyridine (0.04

M) in solution in 40 ml. of absolute alcohol. The reaction is maintainedfor one hour at room temperature. 7.55 g. of diethylchlorothiophosphate(0.04 M) are then added at room temperature, and the mixture is thenrefluxed for one hour.

The sodium chloride is filtered otf and the alcohol removed. The residueis taken up with 100 ml. of chloroform and washed with 80 ml. of 5%sodium bicarbonate, and then twice with 80 ml. of distilled water. It isthen dried over magnesium sulfate. The chloroform is then removed andthe oil is distilled under high vacuum. The resulting oil (yield, 63.5%;Weight, 7.5 g.) has a very pale yellow color and the following physicalconstants:

Boiling point, 0.006 mm. Hg C-.. 112 20 1.5235

Analysis.-Calculated for C H CINO PS (percent): C, 40.61; H, 5.07; N,4.73; P, 10.49. Found (percent): C, 40.86; H, 4.84; N, 4.78; P, 10.45.

EXAMPLE 9 O-ethyl and -3 (chloro-2-methyl-6)pyridyldimethylamidophosphate CzHsO The sodium ethoxide prepared from 0.9 g.(0.04 M) of sodium and 40 ml. of absolute alcohol is added to 5.75 g.(0.04 M) of chloro-2-hydroxy-3-methyl-6-pyridine in solution in 40 ml.of absolute alcohol. The reaction is carried on for one hour at roomtemperature. 6.85 g. of ethyl-dimethylamido-chlorophosphate (0.04 M) arethen added at room temperature, and the reaction mixture is thenrefluxed for one hour.

The sodium chloride is filtered, and the alcohol removed. The residue istaken up with 100 ml. of chloroform, and then washed once with 80 ml. ofsodium bicarbonate and once with 80 ml. of distilled water. It is thendried over magnesium sulfate. The chloroform is then removed, and theoil is distilled under high vacuum. The resulting oil is colorless.

Analysis-Calculated for C H CIN O P (percent): C, 43.08; H, 5.74; N,10.05; P, 11.13. Found (percent): C, 43.12; H, 6.04; N, 9.91; P, 11.12.

EXAMPLE 10 O-ethyland O-3 (ch1oro-2-methyl-6)pyridylphenylthiophosphonate The sodium ethoxide prepared from 0.8 g. (0.035 M)of sodium and 40 ml. of absolute alcohol is added to 5 g. (0.035 M) ofchloro-2-hydroxy-3-methyl-6-pyridine in solution in 40 ml. of absolutealcohol. The reaction is maintained for one hour at ordinary roomtemperature. 7.7 g. (0.035 M) of ethyl-phenylchlorothiophosphonate arethen added at ordinary temperature, and the reaction mixture is refluxedfor one hour.

The sodium chloride is filtered, and the alcohol removed. The residue istaken up with 100 ml. of chloroform, and washed once with 80 ml. of 5%sodium bicarbonate solution, and then with 80 ml. of distilled water. Itis then dried over magnesium sulfate.

Analysis.Calculated for C H CINO PS (percent): C, 51.30; H, 4.58; N,4.27; P, 9.46. Found (percent): C, 51.33; H, 4.63; N, 4.18; P, 9.48.

EXAMPLE l1 O-O-diethyl and O-3 (bromo-2-methyl-6)pyridyl phosphate CgHsOB 1' CH3 The sodium ethoxide prepared from 0.8 g. (0.035 M) of sodiumand 40 ml. of absolute alcohol is added to 6.6 g. (0.035 M) of bromo2-hydroxy-3-methyl-6-pyridine in soltuion in 40 ml. of absolute alcohol.The reaction is carried on for one hour at room temperature. 6.05 g. ofdiethylchlorophosphate 0.035 M) are then added at ordinary temperature,and the mixture is refluxed for one hour.

The sodium chloride is filtered, and the alcohol removed. The residue istaken up with 100 ml. of chloroform, and then washed with ml. of 5%sodium bicarbonate, after which it is washed again with 80 ml. ofdistilled water and dried over magnesium sulfate. The chloroform isremoved, and the resulting oil is kept raw.

Analysis.--Calculated for C H BrNO P (percent): C, 37.03; H, 4.63; N,4.32; P, 9.56. Found (percent): C, 36.95; H, 4.96; N, 4.30; P, 9.48.

EXAMPLE 12 O-O-diethyl and O-3 (chloro-2-nitro-4-methyl-6)pyridylphosphate N/ CH3 The sodium ethoxide prepared from 0.8 g. (0.035 M) ofsodium and 40 ml. of absolute alcohol is added to 6.6 g. (0.035 M) ofchloro 2-hydroxy-3-nitro-4-methyl-6-pyridine in solution in 40 ml. ofabsolute alcohol. The reaction is carried on for one hour'at ordinarytemperature. 6.05 g. (0.035 M) of diethylchlorophosphate are then addedat room temperature, and the mixture is then refluxed for one hour.

The sodium chloride is filtered, and the alcohol removed, as bydistillation. The residue is then taken up with ml. of chloroform, andwashed with 80 ml. of 5% sodium bicarbonate, after which it is washedagain with 80 ml. of distilled water and dried over magnesium sulfate.

The chloroform is then removed, and the resulting oil is kept raw. It isorange yellow, and its index is:

zo 1.4915 Weight g 7.9 Yield percent 69.5

Compounds corresponding to the formula:

X Y i -o Rso I R N/ H:

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EXAMPLE .13

Test on Musca domestica Ten adult flies, 4-5 days old, are disposed in aPet ox provided with a netting lid. The box is treated di- 55 Compound 0Compound D both in the laboratory and in greenhouses. The followinexamples, which are not restrictive, describe the experimentationconditions and the results obtained, with the compounds of thisinvention as compared with known compounds hav Compound A Compound Bfectly by spraying thereon cc. of a solution in acetone of the activematerial to be tested.

The numbers of flies dead and alive are counted one hour after thetreatment. Under such conditions, products Nos. 8, 9, 14, 15, 16, 21,22, 23 and 42 give 100% mortality for the flies with a concentration of0.05 g./l., and products Nos. 3, 10, 13, 27, and 37 give 100% mortalityat a concentration of 0.1 g./l. By way of comparison, known Compounds Aand B require a concentration of 0.5 g./l. to obtain a similar result.Under the same conditions, DDT requires a concentration of 1 g./l. toobtain a similar result.

EXAMPLE 14 Test on Ephestia kuhnielle A few drops (3) of an acetonesolution of the active material to be tested are deposited onto an azymecachet. The acetone is then allowed to evaporate, and eggs of Ephestiakuhnielle are disposed on said cachet, and covered with a glass plate toprevent any escape. A mortality check is efiected 10 days later.

Under such conditions, products Nos. 9 and 40 give 100% mortality at aconcentration of 0.0005 g./l. Products Nos. 3, 11, 12, 21 and 26 give100% mortality at a concentration of 0.001 g./l. By way of comparison,known Compounds A and C require a concentration of 0.01 g./l. forobtaining an 80% mortality, and Compounds B and C require aconcentration of 0.1 g./1. for obtaining 100% mortality Among theinsecticide compounds widely used heretofore, DDT and a-naphthylN-methylcarbamate (carbaryl) require a concentration of 0.1 g./l. inorder to obtain a similar result.

EXAMPLE 15 Test on Tetranychus urticae Bean plants infested withTetranychus urticae are treated directly by means of a compressed airsprayer filled with a solution of the active material to be tested. Themortality check is made by comparison with a reference series ofuntreated bean plants.

Under such conditions, at a concentration of 50 g./hl., Compounds Nos.3, 5, 8, 9, 10, 11, 12, 13, 14, 15, 16, 19, '22, 23, 24, 25, 26, 36, 37and 40 bring about a 100% mortality of the Acaridae.

EXAMPLE 16 Test on Blatella germamca Five adult cockroaches are disposedin a Petri box provided with a netting lid. The box is treated directlyby means of a spraying tower which sprays 5 cc. of an acetone solutionof the active material being tested, at various concentrations. Theresulting mortality obtained after treatment is then noted.

Under such conditions, Compounds Nos. 3, 5, 8, 10, 15, 21, 22 and 42give 100% mortality among the cockroaches at a concentration of 0.1g./l. Under the same conditions, known Compounds A and B require aconcentration of l g./I. to obtain the same result. Under the sameconditions, well-known insecticides, such as azinphosethyl [0,0 diethylS-(4, oxo l, 2, 3 benzotriazin-3 {4 H]y1 methyl)phosphorodithicate],malathion [S 1, 2 di(ethoxycarbonyl)ethyldimethylphosphorothiolothionate], or ronnel [0,0 dimethylO-(2,3,4-trich1orophenyl) phosphorothioate] should be used atconcentrations of the order of one gram/liter to bring about a completedestruction of cockroaches.

EXAMPLE 17 Test on Coenorhabditis elegans 10 cc. of a solution of thecompound to be tested are poured into a 250 cc. screw-cap powder-box.3-4 drops of a concentrated suspension of nematodes (Coenorhabditiselegans) 4 days old, are then added. After 48 hours,

a check for the mortality rate is effected by means of a binocularmagnifying glass.

Under such conditions, products Nos. 1, 3, 5, 7, 8, 9, 10, 11, 12, 13,14, 15, 16, 19, 20, 21, 22, 23, 25 and 37 give mortality of thenematodes at a concentration of 0.1 g./l.

Under the same conditions, but at a concentration ten times less (0.01g./l.), products Nos. 3, 7, 8, 10, 14, 15, 16, 19, 21, 22 and 42 give100% mortality of the nematodes.

For all practical purposes, the compounds of this invention shouldseldom be used in the pure state, except for very low volumeapplications (U.L.V. treatments). Most often, these active materials aremixed with various ad juvants and carriers, or liquid and/or soliddiluents, so as to obtain formulations suitable for the utilizationrequirements and the character of the problem to be solved. Suchformulations may be employed in the form of granules, powdering powders,wettable powders or solutions adapted to be emulsified. The preparationof such formulations pertains to well-known techniques, which are, inparticular, described in published works such as Chemistry of thePesticides, by D. E. H. Frear, 3rd ed., pp. 409'- The polyvalent actionof the compounds of this invention enables them to be used in fightingagainst the parasites of various crops in the agicultural,arboricultural and viticultural fields, as well as in the household orpublic health fields.

It will be understood that changes may be made in the details offormulations and operation without departing from the spirit of theinvention, especially as defined in the following claims.

We claim: 1. A compound having the formula \P---O R20/ R wherein R isselected from the group consisting of C to C alkyl, C to C haloalkyl, Cto 0., alkoxy, phenyl and phenoxy; R is C to C alkyl or C to Chaloalkyl; R is halogen, R is hydrogen and X is S or O.

2. A compound as defined in claim 1 wherein R is C to 0., alkyl and R isC to 0., alkyl.

3. A compound having the formula i -o R20 I R N/ CH:

5. A compound as defined in claim 3 wherein the compound has the formulaC zHy- 0 01 on, N

11 12 6. A compound as defined in claim 3 wherein the com- 9. A compoundas defined in claim 3 wherein the compound has the formula pound has theformula 63H; cmol-cm-o (J r -o P-0 o,m0 G1 I 5 CH:CICH:O I m 7. Acompound as defined in claim 3 wherein the com- References Cited poundhas the formula UNITED STATES PATENTS @fi 3,478,037 11/1969 Fest et a1.260-294.8 K P 3,669,975 6/1972 Demosay et a1. 260-294.8 K CHPO/ 13,535,325 10/1970 Gubler et al. 260294.9 K

N ALAN L. ROTMAN, Primary Examiner 8. A compound as defined in claim 3wherein the com- I U 8 C1 X R pound has the formula 71-94; 260-496 R,297 P; 424-263 @i /P-O I 2 5-0 01

